Despite a widespread belief that marijuana (MJ) impairs driving, the negative impact of acute MJ use on driving performance has been elusive and difficult to replicate. Most driving studies use daylight environments and dry road conditions. Driving after dark when visibility is diminished and/or on icy/snowy roads may further tax driving skills to reveal important deficits. Use of this more challenging, yet realistic scenario may provide a more sensitive, reproducible measure of driving impairment. Functional magnetic resonance imaging (fMRI) will be used during these novel simulated driving scenarios to elucidate the impact of marijuana on known driving neural circuitry. Occasional marijuana users (n=24) will participate in this within-subject, repeated measures design. In a randomized order and in separate testing sessions, participants will receive a placebo, 200 mc/kg, or 300 mc/kg vaporized marijuana via a paced inhalation protocol. Participants will drive in four simulated environments: daylight with dry roads, daylight with icy roads, nighttime with dry roads, and nighttime with icy roads. Under normal road conditions, participants under the influence of marijuana are expected to show a compensatory decrease in speed. Healthy, non-intoxicated volunteers usually slow down in both icy and nighttime conditions. We hypothesize that MJ participants will fail to show such slowing under sub-optimal driving conditions. We further hypothesize brain regions rich in cannabinoid receptors and involved in procedural learning (e.g., the cerebellum) will show altered neural connectivity, while regions with few cannabinoid receptors (e.g., primary visual area) or areas with less involvement in procedural learning (e.g., amygdala) will remain unaffected. Identification of replicable driving scenarios will be useful in future research establishing a behavioral threshold at which driving becomes impaired by marijuana. Identification of the driving neural circuitry altered by marijuana intoxication will aid in understanding whether the impact of marijuana on driving is primarily due to decision making, perceptual distortions, motor coordination, or procedural skill deficits. Impaired neural circuitry involved in decision-making and judgment will have more serious public health consequences as persons under the influence of marijuana may be more likely to continue driving despite intoxication. PUBLIC HEALTH RELEVANCE: Despite a widespread belief that it is harmful, the negative impact of acute marijuana use on driving performance has been difficult to document in repeatable research studies. Most studies, however, evaluate driving during daylight hours with dry road conditions. Driving after dark when visibility is diminished and/or on icy, slippery roads as proposed in this study may provide a more sensitive, reproducible measure of driving impairment under the influence of marijuana. Functional magnetic resonance imaging will provide further insight into how marijuana impairs the neural circuitry involved in driving.